May 20, 2019, 06:49:55 PM
Forum Rules: Read This Before Posting


Topic: Imine formation from aldehyde and amine  (Read 14621 times)

0 Members and 1 Guest are viewing this topic.

Offline linh_ngt

  • Regular Member
  • ***
  • Posts: 26
  • Mole Snacks: +0/-0
  • Gender: Female
Imine formation from aldehyde and amine
« on: November 09, 2012, 11:42:47 AM »
Dear all member,
As I know, imine could be easily formed by reaction of aldehyde and amine, but when i carry out this reaction, it doesnt work and I'm really confused.
My reaction conditions: starting materials (1eq), amine (1.5 eq), MgSO4 (4eq), dry Ch2Cl2 mixed together and kept at 30 -40oC, put overnight but when I check on TLC, there's still starting material left. Even when I try to treat the reaction (just to obtain the product), purify by CC, I can not have desire product. Dont know why because this's a simple reaction??
And I also try this reaction using microwave, but no effective :-<
Is there any helpful opinion? I'm quite confused. And actually, i used directly starting material (aldehyde) from previous reaction, without treatment ( using oxalyl chloride, DMSO, dry CH2Cl2)
Thank you a lot for your comments!
43 <3 <3

Offline discodermolide

  • Chemist
  • Sr. Member
  • *
  • Posts: 5038
  • Mole Snacks: +404/-70
  • Gender: Male
    • My research history
Re: Imine formation from aldehyde and amine
« Reply #1 on: November 09, 2012, 11:49:17 AM »
There is water formed in this reaction, you need to remove it. Add anhydrous magnesium sulphate to your DCM solution, and stir.
Imines are probably not stable to TLC, so be careful when interpreting tlc results. Same goes for CC. Use NMR to judge if the reaction is complete. Don't isolate it, remove the solvent and use it directly. I have a few methods for making various imines of amino acids with aldehydes.
Try this: (Note aden of Et3N is to generate the free amino group so it can react.
A suspension of the gylcine ester hydrochloride salt (other salts can also be used, for example tosylate salts) (1 equivalent) was stirred in methylene chloride for ten minutes and treated with 10 equivalents of anhydrous magnesium sulphate, and stirring continued for 1 hour at room temperature. A solution of the aldehyde (1 equivalent) in methylene chloride was added within 5 minutes at room temperature followed by dropwise addition of triethylamine or a similar tertiary organic base (2 equivalents). Stirring was continued for 20 hours at room temperature, and the mixture was filtered. The solvent was removed in vacuum to give an oily solid. Tert-Butyl-methyl ether was added slowly while stirring to crystallise the triethylamine hydrochloride, which was removed by filtration after stirring the mixture for 1 hour at room temperature. The solvent was then removed from the filtrate to give the desired imine as an oil, or in some cases a solid which were used without further purification.

Yields very very high >98%.
Development Chemists do it on Scale, Research Chemists just do it!
My Research History

Offline linh_ngt

  • Regular Member
  • ***
  • Posts: 26
  • Mole Snacks: +0/-0
  • Gender: Female
Re: Imine formation from aldehyde and amine
« Reply #2 on: November 09, 2012, 11:58:36 AM »
There is water formed in this reaction, you need to remove it. Add anhydrous magnesium sulphate to your DCM solution, and stir.
Imines are probably not stable to TLC, so be careful when interpreting tlc results. Same goes for CC. Use NMR to judge if the reaction is complete. Don't isolate it, remove the solvent and use it directly. I have a few methods for making various imines of amino acids with aldehydes. I can post one if you wish.
Yes, I use anhydrous MgSO4 and dry CH2Cl2 already and I think that'll be effective to remove water. Even when I treat the reaction, I mean that I just filtrate to remove MgSO4, evaporate to remove CH2Cl2 then check it on NMR,  but still can not observe the desire product :-<
Of course I thank you a lot for your post, also your comment about my reaction :)
43 <3 <3

Offline discodermolide

  • Chemist
  • Sr. Member
  • *
  • Posts: 5038
  • Mole Snacks: +404/-70
  • Gender: Male
    • My research history
Re: Imine formation from aldehyde and amine
« Reply #3 on: November 09, 2012, 12:02:17 PM »
The hit it harder. Use toluene and Dean-Stark out the water formed. I assume you can do this on a reasonable scale?
Development Chemists do it on Scale, Research Chemists just do it!
My Research History

Offline linh_ngt

  • Regular Member
  • ***
  • Posts: 26
  • Mole Snacks: +0/-0
  • Gender: Female
Re: Imine formation from aldehyde and amine
« Reply #4 on: November 09, 2012, 12:16:17 PM »
The hit it harder. Use toluene and Dean-Stark out the water formed. I assume you can do this on a reasonable scale?
I also think about this way. But I just wanna try with small amount of aldehyde, so I think Dean-stark's not suitable for this case?
43 <3 <3

Offline discodermolide

  • Chemist
  • Sr. Member
  • *
  • Posts: 5038
  • Mole Snacks: +404/-70
  • Gender: Male
    • My research history
Re: Imine formation from aldehyde and amine
« Reply #5 on: November 09, 2012, 12:17:44 PM »
The aldehyde must be readily available? If so you can do a larger reaction.
If not try anhydrous copper sulphate.
Development Chemists do it on Scale, Research Chemists just do it!
My Research History

Offline fledarmus

  • Chemist
  • Sr. Member
  • *
  • Posts: 1676
  • Mole Snacks: +203/-28
Re: Imine formation from aldehyde and amine
« Reply #6 on: November 09, 2012, 06:58:17 PM »
You may need to increase temperature. This usually makes drying agents less effective, so you might need to switch to molecular sieves, or if your temperature is high enough, to drying tubes or Dean-Stark traps.

Offline orgopete

  • Chemist
  • Sr. Member
  • *
  • Posts: 2636
  • Mole Snacks: +213/-71
    • Curved Arrow Press
Re: Imine formation from aldehyde and amine
« Reply #7 on: November 09, 2012, 11:39:56 PM »
I can imagine a lot that can occur in this reaction, what are you finding? The description is as though it is no reaction. Is that really true or are you seeing different products than expected?
Author of a multi-tiered example based workbook for learning organic chemistry mechanisms.

Offline Dan

  • Retired Staff
  • Sr. Member
  • *
  • Posts: 4716
  • Mole Snacks: +467/-72
  • Gender: Male
  • Organic Chemist
    • My research
Re: Imine formation from aldehyde and amine
« Reply #8 on: November 10, 2012, 11:05:09 AM »
when I check on TLC, there's still starting material left. Even when I try to treat the reaction (just to obtain the product), purify by CC, I can not have desire product. Dont know why because this's a simple reaction??

I can't see your picture, but I also suspect the problem is that your imine is unstable on silica, and decomposes back to the starting materials as soon as you spot it on a TLC plate or load it onto a silica column:

Quote from: discodermolide
Imines are probably not stable to TLC, so be careful when interpreting tlc results. Same goes for CC. Use NMR to judge if the reaction is complete. Don't isolate it, remove the solvent and use it directly.

The reaction may be working perfectly well, you are just using an inappropriate technique for monitoring/purification. What does the crude NMR look like?
My research: Google Scholar and Researchgate

Offline linh_ngt

  • Regular Member
  • ***
  • Posts: 26
  • Mole Snacks: +0/-0
  • Gender: Female
Re: Imine formation from aldehyde and amine
« Reply #9 on: November 11, 2012, 07:32:09 PM »
Thank everyone,
actually, i just increase temp to nearly 50oC, under argon conditions and MgSO4.
As u say, maybe when i check reaction on TLC, imine could be changed into starting material. I conclude that because when I test the crude product on NMR, I dont see the starting material left but there's also no desire product (my treatment: filtration for removing MgSO4 and evaporate for removing CH2Cl2, then check by NMR).
Here I attach my reaction file. Thank u a lot for your comments!
43 <3 <3

Offline Dan

  • Retired Staff
  • Sr. Member
  • *
  • Posts: 4716
  • Mole Snacks: +467/-72
  • Gender: Male
  • Organic Chemist
    • My research
Re: Imine formation from aldehyde and amine
« Reply #10 on: November 12, 2012, 03:27:41 AM »
when I test the crude product on NMR, I dont see the starting material left but there's also no desire product

Just to make absolutely sure, you should treat your CDCl3 with anhydrous K2CO3. There can be enough HCl in chloroform to catalyse the decomposition of some imines - I have personally experienced this problem and wasted a significant amount of time because I thought my reactions were not working when in fact they were working perfectly.
My research: Google Scholar and Researchgate

Offline linh_ngt

  • Regular Member
  • ***
  • Posts: 26
  • Mole Snacks: +0/-0
  • Gender: Female
Re: Imine formation from aldehyde and amine
« Reply #11 on: November 12, 2012, 05:10:49 AM »
Well, i used dry CH2Cl2 for treatment process.
Here I show you the NMR data of the crude product (without purification).
Could you give some comments for that?
43 <3 <3

Offline discodermolide

  • Chemist
  • Sr. Member
  • *
  • Posts: 5038
  • Mole Snacks: +404/-70
  • Gender: Male
    • My research history
Re: Imine formation from aldehyde and amine
« Reply #12 on: November 12, 2012, 05:56:01 AM »
I do not see the data!
Development Chemists do it on Scale, Research Chemists just do it!
My Research History

Offline linh_ngt

  • Regular Member
  • ***
  • Posts: 26
  • Mole Snacks: +0/-0
  • Gender: Female
Re: Imine formation from aldehyde and amine
« Reply #13 on: November 12, 2012, 06:29:46 AM »
oops, I attach the data again ( jpg file)
43 <3 <3

Offline discodermolide

  • Chemist
  • Sr. Member
  • *
  • Posts: 5038
  • Mole Snacks: +404/-70
  • Gender: Male
    • My research history
Re: Imine formation from aldehyde and amine
« Reply #14 on: November 12, 2012, 07:25:34 AM »
That NMR looks very strange, not much imine I think.
Development Chemists do it on Scale, Research Chemists just do it!
My Research History

Sponsored Links